Effect of age on the toxicity and metabolism of ethylene glycol monobutyl ether (2-butoxyethanol) in rats.

Heavy production as well as the diversity of 2-butoxyethanol (BE) uses, which include preparation of products intended for household uses, pose a high risk of human exposure to BE. The current studies were designed to investigate the acute toxicity of BE and to evaluate the effect of age on BE-induced toxicity in F344 male rats. Data presented in this report show that BE causes severe acute hemolytic anemia resulting in significant increases in the concentration of free plasma hemoglobin. Secondary to the hemolytic effects, BE also caused hemoglobinuria as well as histopathologic changes in the liver and kidney. These effects of BE were dose- and time-dependent. Further, both the hemolytic effects and the secondary effects of BE were age dependent with older rats being more sensitive than younger rats. The metabolic basis of the greater susceptibility of older rats to BE-induced toxicity was investigated by comparing BE metabolism in adult (9- to 13-week-old) and young (4- to 5-week-old) rats. These studies revealed that there was a significantly higher portion of the administered dose eliminated by young rats as CO2 as compared to that eliminated by older rats. Similarly, a significantly higher portion of the administered dose was excreted in the urine of young rats. HPLC analysis of the urinary metabolites of BE in adult and young rats showed that the ratio of butoxyacetic acid (BAA)/BE-glucuronide + BE - sulfate (previously thought to reflect an activation/detoxification index of BE; see text) was significantly higher in older rats. We currently believe that the increase in the activation/detoxification index in older rats is caused by decreased degradation of BAA to CO2 (as evident by the lower percentage of the dose excreted as CO2 by older rats) and by depressed urinary excretion of BAA (as evident from the lower percentage of the dose excreted in the urine of older rats.